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CCR2、CX3CR1、RANTES和SDF1基因多态性影响津巴布韦儿童群体中的HIV感染。

CCR2, CX3CR1, RANTES and SDF1 genetic polymorphisms influence HIV infection in a Zimbabwean pediatric population.

作者信息

Mhandire Kudakwashe, Duri Kerina, Kandawasvika Gwendoline, Chandiwana Precious, Chin'ombe Nyasha, Kanyera Russell Batsirai, Stray-Pedersen Babill, Dandara Collet

机构信息

Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.

出版信息

J Infect Dev Ctries. 2014 Oct 15;8(10):1313-21. doi: 10.3855/jidc.4599.

DOI:10.3855/jidc.4599
PMID:25313609
Abstract

INTRODUCTION

There is growing evidence that polymorphisms in chemokine and chemokine receptor genes influence susceptibility to HIV infection and disease progression. However, not much is documented about the prevalence and effects of chemokine and chemokine receptor gene variations in the Zimbabwean population despite the high burden of HIV/AIDS in the country. This study therefore describes polymorphisms in CCR2, CX3CR1, SDF1 and RANTES genes in a Zimbabwean pediatric population and their effects on HIV infection in children born to HIV-infected mothers.

METHODOLOGY

A total of 106 children between seven and nine years of age comprising 70 perinatally exposed to HIV (34 born infected [EI] and 36 born uninfected [EU]) and 36 unexposed and uninfected (UEUI) controls were recruited. Six allelic variants in four genes were genotyped using PCR-RFLP and sequencing.

RESULTS

Frequencies for minor alleles in the HIV uninfected groups (EU and UEUI) were CCR2 190A (16%), SDF1 801A (2%), CX3CR1 745A (9%), CX3CR1 839T (0%), RANTES In 1.1C (20%), and RANTES -403A (44%). There were significant differences between the EI and EU groups in the distribution of CCR2 190G/A genotype (15% versus 39%, respectively, p = 0.02) and CCR2 190G/A-CX3CR1 745G/G genotype combination (0% versus 33%, respectively, p = 0.002).

CONCLUSIONS

Our findings suggest that chemokine and chemokine receptor gene variants seem to play an important role in the dynamics of HIV infection and could be used as drug or vaccine targets.

摘要

引言

越来越多的证据表明,趋化因子和趋化因子受体基因的多态性会影响对HIV感染和疾病进展的易感性。然而,尽管津巴布韦的HIV/AIDS负担很重,但关于趋化因子和趋化因子受体基因变异在津巴布韦人群中的流行情况和影响的文献报道并不多。因此,本研究描述了津巴布韦儿童人群中CCR2、CX3CR1、SDF1和RANTES基因的多态性及其对HIV感染母亲所生孩子感染HIV的影响。

方法

共招募了106名7至9岁的儿童,其中70名是围产期暴露于HIV的儿童(34名出生时感染[EI],36名出生时未感染[EU]),36名未暴露且未感染(UEUI)的对照儿童。使用PCR-RFLP和测序对四个基因中的六个等位基因变体进行基因分型。

结果

HIV未感染组(EU和UEUI)中次要等位基因的频率分别为CCR2 190A(16%)、SDF1 801A(2%)、CX3CR1 745A(9%)、CX3CR1 839T(0%)、RANTES In 1.1C(20%)和RANTES -403A(44%)。EI组和EU组在CCR2 190G/A基因型分布(分别为15%和39%,p = 0.02)以及CCR2 190G/A-CX3CR1 745G/G基因型组合分布(分别为0%和33%,p = 0.002)上存在显著差异。

结论

我们的研究结果表明,趋化因子和趋化因子受体基因变体似乎在HIV感染动态中起重要作用,可作为药物或疫苗靶点。

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